In order to understand the genesis of birth defects our approach is to study intensely a very simple situation. Acetazolamide given to pregnant rodents causes absence of digit 5 of the right hand. The only known action of this drug is to inhibit the enzyme carbonic anhydrase. Thus we have been and will continue to explore all aspects of carbonic anhydrase and its inhibition in rat and mouse embryos. Most interesting for development in general has been the finding of unique carbonic anhydrase isozymes in young embryos which switch to adult type isozymes at developmental stages similar to hemoglobin. Aspirin administration to pregnant rodents causes an extra first digit predominantly on the right hindlimb. Evidence has indicated that prostaglandin synthesis is inhibited by aspirin leading to vasoconstriction of hindlimb vessels. The right hindlimb is more severely affected because the vessel supplying this limb is half the size of that supplying the left hindlimb. Future work will attempt to more clearly elucidate the developmental role of prostaglandins. The central role of DNA in development has led us to investigations of deoxyribonucleotide pools in rodent embryos. We are now able to accurately measure these pools and determine what effect(s) teratogenic agents have on these important precursors. Future work will attempt to demonstrate regulatory roles of these pools on DNA synthesis and a causative role in certain drug-induced malformations.